WO2008060783A2 - Antagonistes de ccr2 pour le traitement de la fibrose - Google Patents

Antagonistes de ccr2 pour le traitement de la fibrose Download PDF

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Publication number
WO2008060783A2
WO2008060783A2 PCT/US2007/080542 US2007080542W WO2008060783A2 WO 2008060783 A2 WO2008060783 A2 WO 2008060783A2 US 2007080542 W US2007080542 W US 2007080542W WO 2008060783 A2 WO2008060783 A2 WO 2008060783A2
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WO
WIPO (PCT)
Prior art keywords
fibrosis
antibody
mcp
ser
ccl2
Prior art date
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Ceased
Application number
PCT/US2007/080542
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English (en)
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WO2008060783A3 (fr
Inventor
Anuk Das
Lynne Murray
Farhat Syed
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Janssen Biotech Inc
Centocor
Original Assignee
Centocor Ortho Biotech Inc
Centocor
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to AU2007319660A priority Critical patent/AU2007319660A1/en
Priority to CA002665808A priority patent/CA2665808A1/fr
Priority to JP2009531622A priority patent/JP2010505878A/ja
Priority to BRPI0718225-2A2A priority patent/BRPI0718225A2/pt
Priority to EA200970350A priority patent/EA200970350A1/ru
Priority to MX2009003762A priority patent/MX2009003762A/es
Priority to EP07868380A priority patent/EP2068920A2/fr
Priority to US12/442,404 priority patent/US20100074886A1/en
Application filed by Centocor Ortho Biotech Inc, Centocor filed Critical Centocor Ortho Biotech Inc
Publication of WO2008060783A2 publication Critical patent/WO2008060783A2/fr
Publication of WO2008060783A3 publication Critical patent/WO2008060783A3/fr
Priority to IL198005A priority patent/IL198005A0/en
Anticipated expiration legal-status Critical
Priority to NO20091630A priority patent/NO20091630L/no
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A61P33/12—Schistosomicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Definitions

  • CCR2 as defined herein, includes mature receptor protein, polymorphic or allelic variants, and isoforms of a mammalian CCR2 (e.g., produced by alternative splicing or other cellular processes), and modified or unmodified forms of the foregoing (e.g., glycosylated, unglycosylated). Such proteins can be recovered or isolated from a source which naturally produces mammalian CCR2, for example.
  • treating used in this invention means both treatments that comprise “controlling” and “reversing” the functional or histological signs of chronic rejection.
  • Mammals which maybe treated in the present invention include livestock mammals such as cows, houses, etc., domestic animals such as dogs, cats, rats, etc. and humans, preferably humans.
  • MCP-1/CCL2 truncations, variants, mutant proteins or "muteins” having the ability to bind CCR2 and have antagonistic activity may also be used to practice the method of the invention.
  • Variants of homodimer- forming chemokines, such as CCL2, having a single amino acid substitution in the dimerization interface that alters the pattern of hydrogen bonds, so as to result in an obligate monomer that binds to the receptor and has agonistic properties in vitro but which can antagonize natural chemokines and have anti-inflammatory activity in vivo as taught in WO05037305A1 are among the variants useful in practicing the present invention.
  • splenocytes and lymph node cells from immunized mice can be isolated and fused to an appropriate immortalized cell line, such as a mouse myeloma cell line.
  • an appropriate immortalized cell line such as a mouse myeloma cell line.
  • the resulting hybridomas can be screened for the production of antigen-specific antibodies.
  • Antagonists of CCR2 biological activity can be identified using suitable in vitro assays and in vivo models as exemplified hereinbelow.
  • Binding inhibition assays can be used to identify antibodies or fragments thereof which bind CCR2 and inhibit binding of another compound such as a ligand (e.g., MCP-I, MCP-2, MCP-3 and/or MCP -4) to CCR2 or a functional variant.
  • a binding assay can be conducted in which a reduction in the binding of a ligand of CCR2 (in the presence of an antibody), as compared to binding of the ligand in the absence of the antibody, is detected or measured.
  • G protein activity such as hydrolysis of GTP to GDP, or later signaling events triggered by receptor binding, such as induction of rapid and transient increase in the concentration of intracellular (cytosolic) free calcium [Ca2+ ]I
  • G protein activity can be assayed by methods known in the art or other suitable methods (see e.g., Neote, K. et al., Cell, 72: 415-425 1993); Van Riper et al., J. Exp. Med., 177: 851-856 (1993); Dahinden, C. A. et al., J. Exp. Med., 179: 751-756 (1994)).
  • the assay is performed by detecting the directional migration of cells into or through a membrane or filter, in a direction toward increased levels of a compound, from a first surface of the filter toward an opposite second surface of the filter, wherein the filter contains an endothelial cell layer on a first surface.
  • Directional migration occurs from the area adjacent to the first surface, into or through the membrane, towards a compound situated on the opposite side of the filter.
  • concentration of compound present in the area adjacent to the second surface is greater than that in the area adjacent to the first surface.
  • TGFbI The profibrotic role of TGFbI has been well described.
  • TGFbI, PDGF and CCL2- induced TGFbI gene expression (Fig. 4).
  • TGFbI induction by an autocrine loop is known and is supported by the present data with both the non-fibrotic and fibrotic fibroblasts.
  • CCL2 also enhances TGFbI gene expression.
  • the extent of TGFbI gene induction by CCL2 was greater in the fibrotic fibroblasts.
  • X may be Leu, lie, His, Tyr, Phe, or GIn ⁇ 220>
  • Xaa may be GIn or Phe
  • Xaa may be Asp or GIu

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Biochemistry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Transplantation (AREA)
  • Diabetes (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Vascular Medicine (AREA)
  • Neurology (AREA)
  • Microbiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Mycology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Thérapie à antagoniste anti-MCP-1/CCR2 pour le contrôle ou la régression de maladies liées à la fibrose, y compris mais pas seulement la thérapie à antagoniste anti-MCP-1/CCR2 pour la modulation de marqueurs profibrotiques associés aux processsus fibrotiques englobant le dépôt de matrice de collagène et le collapsus alvéolaire.
PCT/US2007/080542 2006-10-05 2007-10-05 Antagonistes de ccr2 pour le traitement de la fibrose Ceased WO2008060783A2 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
EP07868380A EP2068920A2 (fr) 2006-10-05 2007-10-05 Antagonistes de ccr2 pour le traitement de la fibrose
JP2009531622A JP2010505878A (ja) 2006-10-05 2007-10-05 線維症の処置のためのｃｃｒ２アンタゴニスト
BRPI0718225-2A2A BRPI0718225A2 (pt) 2006-10-05 2007-10-05 Antagonistas de ccr2 para tratamento de fibrose
EA200970350A EA200970350A1 (ru) 2006-10-05 2007-10-05 Антагонисты ccr2 для лечения фиброза
MX2009003762A MX2009003762A (es) 2006-10-05 2007-10-05 Antagonistas del receptor cc-quimiocina 2 para el tratamiento de fibrosis.
AU2007319660A AU2007319660A1 (en) 2006-10-05 2007-10-05 CCR2 antagonists for treatment of fibrosis
CA002665808A CA2665808A1 (fr) 2006-10-05 2007-10-05 Antagonistes de ccr2 pour le traitement de la fibrose
US12/442,404 US20100074886A1 (en) 2006-10-05 2007-10-05 Ccr2 antagonists for treatment of fibrosis
IL198005A IL198005A0 (en) 2006-10-05 2009-04-05 Ccr2 antagonists for treatment of fibrosis
NO20091630A NO20091630L (no) 2006-10-05 2009-04-23 CCR2-antagonister for behandling av fibrose

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US82825306P 2006-10-05 2006-10-05
US60/828,253 2006-10-05

Publications (2)

Publication Number Publication Date
WO2008060783A2 true WO2008060783A2 (fr) 2008-05-22
WO2008060783A3 WO2008060783A3 (fr) 2008-10-23

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PCT/US2007/080542 Ceased WO2008060783A2 (fr) 2006-10-05 2007-10-05 Antagonistes de ccr2 pour le traitement de la fibrose

Country Status (17)

Country Link
US (1) US20100074886A1 (fr)
EP (1) EP2068920A2 (fr)
JP (1) JP2010505878A (fr)
KR (1) KR20090074787A (fr)
CN (1) CN101616689A (fr)
AU (1) AU2007319660A1 (fr)
BR (1) BRPI0718225A2 (fr)
CA (1) CA2665808A1 (fr)
CO (1) CO6160339A2 (fr)
EA (1) EA200970350A1 (fr)
EC (1) ECSP099226A (fr)
GT (1) GT200900075A (fr)
IL (1) IL198005A0 (fr)
MX (1) MX2009003762A (fr)
NI (1) NI200900048A (fr)
NO (1) NO20091630L (fr)
WO (1) WO2008060783A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8354431B2 (en) 2007-02-19 2013-01-15 Novartis Ag Aryl carboxylic acid cyclohexyl amide derivatives
US8465413B2 (en) 2010-11-25 2013-06-18 Coloplast A/S Method of treating Peyronie's disease
EP2852411A4 (fr) * 2012-05-22 2016-01-13 Shire Human Genetic Therapies Anticorps anti-ccl2 pour le traitement de la sclérodermie

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Publication number Priority date Publication date Assignee Title
RU2547595C2 (ru) 2008-08-18 2015-04-10 Пфайзер Инк Антитела против ccr2
CN103391931A (zh) * 2011-02-25 2013-11-13 辉瑞有限公司 治疗肝纤维化的方法
CN107099581B (zh) * 2012-03-27 2021-07-13 弗·哈夫曼-拉罗切有限公司 预测、诊断和治疗特发性肺纤维化的方法
WO2013192596A2 (fr) * 2012-06-22 2013-12-27 Sorrento Therapeutics Inc. Protéines de liaison à un antigène qui se lient à ccr2
US9535071B2 (en) 2012-09-07 2017-01-03 The Governors Of The University Of Alberta Methods and compositions for diagnosis of inflammatory liver disease
EP3119401A4 (fr) * 2014-03-21 2017-12-13 Tobira Therapeutics, Inc. Cenicriviroc pour le traitement de la fibrose
JP2019506259A (ja) * 2015-12-11 2019-03-07 ベロ バイオテック エルエルシー 線維症に対処するために一酸化窒素を含むガスを投与するための方法及び装置
JOP20190095A1 (ar) 2016-10-27 2019-04-28 Janssen Pharmaceutica Nv مركبات ببتيد تيروسين-تيروسين الحلقية كمعدلات لمستقبلات الببتيد العصبي y
WO2018106945A1 (fr) 2016-12-07 2018-06-14 Progenity Inc. Procédés, dispositifs et systèmes de détection du tractus gastro-intestinal
EP3554541B1 (fr) 2016-12-14 2023-06-07 Biora Therapeutics, Inc. Traitement d'une maladie du tractus gastro-intestinal avec une chimoikine/un inhibiteur du récepteur de chimiokine
WO2019003159A1 (fr) * 2017-06-27 2019-01-03 Neuracle Science Co., Ltd. Utilisation d'anticorps anti-fam19a5 pour le traitement de la fibrose
EP3883635A1 (fr) 2018-11-19 2021-09-29 Progenity, Inc. Méthodes et dispositifs pour traiter une maladie au moyen d'une biothérapie
CN115666704B (zh) 2019-12-13 2025-09-26 比特比德科有限责任公司 用于将治疗剂递送至胃肠道的可摄取装置

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SE9600820D0 (sv) * 1996-03-01 1996-03-01 Pharmacia Ab Antibodies and their use
GB9716657D0 (en) * 1997-08-07 1997-10-15 Zeneca Ltd Chemical compounds
US6696550B2 (en) * 1998-07-23 2004-02-24 Millennium Pharmaceuticals, Inc. Humanized anti-CCR2 antibodies and methods of use therefor
US6312689B1 (en) * 1998-07-23 2001-11-06 Millennium Pharmaceuticals, Inc. Anti-CCR2 antibodies and methods of use therefor
CA2373942A1 (fr) * 1999-05-18 2000-11-23 Teijin Limited Remedes ou prophylactase contre les maladies associees a des chimiokines
GB0016138D0 (en) * 2000-06-30 2000-08-23 Novartis Ag Organic compounds
AU2001292301A1 (en) * 2000-10-11 2002-04-22 Daiichi Pharmaceutical Co., Ltd. Novel drugs for liver diseases
US6670364B2 (en) * 2001-01-31 2003-12-30 Telik, Inc. Antagonists of MCP-1 function and methods of use thereof
CA2572289A1 (fr) * 2004-06-30 2006-08-17 Centocor, Inc. Anticorps anti-mcp-1, compositions, procedes et utilisations
US8114964B2 (en) * 2005-05-19 2012-02-14 Centocor, Inc. Anti-MCP-1 antibodies, compositions, methods and uses
WO2006125201A2 (fr) * 2005-05-19 2006-11-23 Centocor, Inc. Anticorps anti-muteines mcp-1 biotine-pegylees, compositions, procedes et utilisations correspondants

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8354431B2 (en) 2007-02-19 2013-01-15 Novartis Ag Aryl carboxylic acid cyclohexyl amide derivatives
US8465413B2 (en) 2010-11-25 2013-06-18 Coloplast A/S Method of treating Peyronie's disease
EP2852411A4 (fr) * 2012-05-22 2016-01-13 Shire Human Genetic Therapies Anticorps anti-ccl2 pour le traitement de la sclérodermie
CN105854015A (zh) * 2012-05-22 2016-08-17 夏尔人类遗传性治疗公司 用于治疗硬皮病的抗ccl2抗体

Also Published As

Publication number Publication date
NO20091630L (no) 2009-07-03
JP2010505878A (ja) 2010-02-25
CO6160339A2 (es) 2010-05-20
ECSP099226A (es) 2009-06-30
EA200970350A1 (ru) 2009-12-30
EP2068920A2 (fr) 2009-06-17
MX2009003762A (es) 2009-07-10
BRPI0718225A2 (pt) 2013-11-12
IL198005A0 (en) 2011-08-01
CA2665808A1 (fr) 2008-05-22
WO2008060783A3 (fr) 2008-10-23
GT200900075A (es) 2010-05-14
CN101616689A (zh) 2009-12-30
KR20090074787A (ko) 2009-07-07
AU2007319660A1 (en) 2008-05-22
NI200900048A (es) 2010-02-01
US20100074886A1 (en) 2010-03-25

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